rs606231311
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Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_003051.4(SLC16A1):βc.747_750delβ(p.Asn250SerfsTer5) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000124 in 1,614,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 32)
Exomes π: 0.000012 ( 0 hom. )
Consequence
SLC16A1
NM_003051.4 frameshift
NM_003051.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.22
Genes affected
SLC16A1 (HGNC:10922): (solute carrier family 16 member 1) The protein encoded by this gene is a proton-linked monocarboxylate transporter that catalyzes the movement of many monocarboxylates, such as lactate and pyruvate, across the plasma membrane. Mutations in this gene are associated with erythrocyte lactate transporter defect. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.751 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
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Variant 1-112917655-GATTA-G is Pathogenic according to our data. Variant chr1-112917655-GATTA-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 160371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC16A1 | NM_003051.4 | c.747_750del | p.Asn250SerfsTer5 | frameshift_variant | 4/5 | ENST00000369626.8 | |
SLC16A1 | NM_001166496.2 | c.747_750del | p.Asn250SerfsTer5 | frameshift_variant | 4/5 | ||
SLC16A1 | XM_047428789.1 | c.747_750del | p.Asn250SerfsTer5 | frameshift_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC16A1 | ENST00000369626.8 | c.747_750del | p.Asn250SerfsTer5 | frameshift_variant | 4/5 | 1 | NM_003051.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251426Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461890Hom.: 0 AF XY: 0.00000963 AC XY: 7AN XY: 727246
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152250Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74384
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ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | This sequence change creates a premature translational stop signal (p.Asn250Serfs*5) in the SLC16A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC16A1 are known to be pathogenic (PMID: 25390740). This variant is present in population databases (rs606231311, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with SLC16A1-related conditions (PMID: 25390740). ClinVar contains an entry for this variant (Variation ID: 160371). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Oct 10, 2022 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34758253, 25390740) - |
Monocarboxylate transporter 1 deficiency, autosomal dominant Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 13, 2014 | - - |
Ketoacidosis due to monocarboxylate transporter-1 deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Dec 14, 2022 | PVS1, PM2 - |
Metabolic myopathy due to lactate transporter defect Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Genomics England Pilot Project, Genomics England | - | - - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at